Zika Virus Inhibitors Based on a 1,3-Disubstituted 1H-Pyrazolo[3,4-d]pyrimidine-amine Scaffold

Eunkyung Jung, Ruben Soto-Acosta, Robert J. Geraghty, Liqiang Chen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


To search for Zika virus (ZIKV) antivirals, we have further explored previously reported 7H-pyrrolo[2,3-d]pyrimidines by examining an alternative substitution pattern of their central scaffold, leading to compound 5 with low micromolar antiviral activity. To circumvent the synthetic difficulties associated with compound 5, we have exploited a 1H-pyrazolo[3,4-d]pyrimidine scaffold and performed structure-activity relationship studies on its peripheral rings A and B. While ring B is less sensitive to structural modifications, an electron-withdrawing group at the para position of ring A is preferred for enhanced antiviral activity. Overall, we have not only discovered an alternative substitution pattern centered on a 1H-pyrazolo[3,4-d]pyrimidine scaffold but also generated anti-ZIKV compounds including 6 and 13, which possess low micromolar antiviral activity and relatively low cytotoxicity. These compounds represent new chemotypes that will be further optimized in our continued efforts to discover anti-ZIKV agents.

Original languageEnglish (US)
Article number6109
Issue number18
StatePublished - Sep 2022

Bibliographical note

Funding Information:
This research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, grant number R21AI151427 (to LC) and a University of Minnesota Academic Health Center Faculty Research Development Grant (to RJG).

Publisher Copyright:
© 2022 by the authors.


  • Zika virus
  • Zika virus inhibitors
  • antiviral agents
  • flavivirus


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